The present invention relates generally to a method of magnetic resonance (MR) imaging and, more particularly, to mapping changes in oxygen level in vivo. The present invention further relates to a method of MRI, and MR spectroscopy for determining oxygenation of heme-proteins in vivo. In vivo oxygen is present primarily in the form of oxy-hemoglobin and oxy-myoglobin. Detection of hemoglobin and myoglobin in the deoxy state can be used to determine oxygen debt and by calculation, pO2 levels may be determined. Deoxy-myoglobin and deoxy-hemoglobin both have unique hyperfine shifted signals over 70 ppm downfield from the water signal which can be used to distinguish them from their oxy counterparts.
When a substance such as human tissue is subjected to a uniform magnetic field (polarizing field B0), the individual magnetic moments of the spins in the tissue attempt to align with this polarizing field, but precess about it in random order at their characteristic Larmor frequency. If the substance, or tissue, is subjected to a magnetic field (excitation field B1) which is in the x-y plane and which is near the Larmor frequency, the net aligned moment, or “longitudinal magnetization”, MZ, may be rotated, or “tipped”, into the x-y plane to produce a net transverse magnetic moment Mt. A signal is emitted by the excited spins after the excitation signal B1 is terminated and this signal may be received and processed to form an image.
When utilizing these signals to produce images, magnetic field gradients (Gx, Gy, and Gz) are employed. Typically, the region to be imaged is scanned by a sequence of measurement cycles in which these gradients vary according to the particular localization method being used. The resulting set of received NMR signals are digitized and processed to reconstruct the image using one of many well known reconstruction techniques.
Typically, MR imaging protocols utilize water content within the subject and properties thereof to develop contrast and thereby image specific regions of the subject. Specifically, conventional MR imaging techniques rely on the relaxation properties of hydrogen atoms of water to provide a means whereby contrast is obtained in the reconstructed image. As such, conventional MR images of tissues employ a combination of spin-lattice (T1) and spin—spin (T2) water relaxation to generate image contrast between tissues.
The imaging techniques we have discussed so far detect signals from “mobile molecules” having “mobile protons.” That is, “direct” MR imaging techniques are predicated upon the “mobile molecules” having “mobile protons,” which have a relatively long T2 relaxation period such that encoding gradients can be established between initial excitation and acquisition for data acquisition before the relaxation signal has decayed to an undetectable state.
However, these techniques are less adapt at imaging “immobile” or “less-mobile molecules” that have “less-mobile protons” with reduced T2 properties, e.g. T2 periods of less than one millisecond (ms). As result, these immobile, or slow moving, molecules contained in macromolecules, cannot be directly imaged. As such, MR imaging techniques have been developed to take advantage of coupling between the immobile protons and the mobile protons of water to allow imaging of these less mobile molecules.
Specifically, the mobile and immobile protons exist in slightly different magnetic environments and, therefore, each can be separately excited. By selectively exciting the immobile protons contained in the macromolecules with a narrow-band RF pulse, magnetization exchange can be induced between the immobile protons and the mobile protons in free water. That is, it is possible to saturate the spins of the immobile protons, which have a much broader absorption lineshape than the spins of the mobile protons, thereby causing the spins of the immobile protons to be transferred to the mobile protons. As such, the non-directly imageable immobile molecules become imageable in accordance with MR imaging technology by observing the interaction of mobile protons in free water molecules. Simply, since the spin state of the immobile protons can be excited to influence the spin state of the mobile protons, these non-directly imageable molecules can be imaged indirectly as a result of their influence on imageable molecules. This process is typically referred to as magnetization transfer (MT) imaging.
Chemical shift can also be used to distinguish chemicals beyond the dominant water signal. Chemical shift data can be collected as single volume elements or as images. Unlike oxy-hemoglobin and oxy-myoglobin, both deoxy-hemoglobin and deoxy-myoglobin have signals well resolved from the dominant water signal (over 70 ppm), and can be directly detected. Unfortunately, low concentrations of these signals, translates into low resolution imaging or single volume detection methods.
It has recently been demonstrated that protons in exchange with water can be detected with amplification by imaging the change in water signal after selective presaturation of the water exchangeable signal. A potentially confounding factor in utilizing these imaging techniques is the so-called MT effect. That is, bound water signals in magnetic exchange with water can overlap the discrete chemical shifts that are the basis of our invention. However, this is not an issue for detecting relative changes in oxygen level with stress or activation, but require additional measurements for absolute concentration images.
Although direct detection of deoxy-myoglobin and deoxy-hemoglobin provide accurate measure of oxygen debt, an amplified response, even at less quantifiable levels, would be desirable. It would therefore be desirable to have a system and method capable of providing images with sufficient sensitivity to imagedeoxy-hemoglobin and deoxy-myoglobin.